Calcium phosphate cements, in which one or more dry components and a liquid are combined to form a flowable, paste-like material that is subsequently capable of setting into a solid calcium phosphate product, hold great promise for use as structural materials in the orthopedic, cranio-maxillofacial, dental and related fields. For example, it is desirable to be able to inject a flowable material into a cancellous bone void and have the material set into a solid calcium phosphate mineral product that is capable of withstanding physiological loads. Materials that set into solid calcium phosphate mineral products are of particular interest as such products can closely resemble the mineral phase of natural bone and are potentially remodelable, making such products extremely attractive for use in orthopedics and related fields.
In view of the great interest in calcium phosphate cements, a variety of different formulations have been developed to date. See the Relevant Literature section infra.
Despite the number of different calcium phosphate cements that have been produced, there is continued interest in the development of new calcium phosphate cements that are particularly suited to a particular type of application. One such cement of interest would be a calcium phosphate cement that produces a flowable material capable of setting into an antimicrobial apatitic product that is suitable for use a cancellous bone structural material.
Relevant Literature
U.S. Pat. No. 5,591,453 describes a silica-based glass carrier for biologically active molecules. Patents of interest describing calcium phosphate cements include: 4,684,673; 5,037,639, 5,683,461; 5,676,976; 5,650,176; 4,108,690 and 5,508,342, as well as 4,880,610; 5,047,031; 5,129,905; 5,336,264; 5,053,212; 5,178,845; 5,580,623; 5,569,442; 5,571,493; 5,496,399; 5,683,667; 5,683,496; and 5,697,981. Also of interest are WO 96/36562 and WO 97/17285.
Constantz et al., "Skeletal Repair by in Situ Formation of the Mineral Phase of Bone," Science (Mar. 24, 1995) 267: 1796-1798, describes a calcium phosphate cement comprising .alpha.-tricalcium phosphate, MCPM, and CaCO.sub.3. Also of interest is: Lemaitre et al., "Setting, Hardening and Resorption of Calcium Phosphate Hydraulic Cements," Rev. Stomatol. Chir. Maxillofac. (1992) 93: 163-165.
Other references of interest include: Takechi et al., "Effects of Added Antibiotics on the Basic Properties of Anti-Washout-Type Fast-Setting Calcium Phosphate Cement," J. Biomed. Mater. Res. (February 1998) 39: 308-316; Bohner et al., "Gentamycin-Loaded Hydraulic Calcium Phosphate Bone Cement as Antibiotic Delivery System," J. Pharm. Sci. (May 1997) 86: 565-572; Hamanishi et al., "A Self-Setting TTCP-DCPD Apatite Cement for Release of Vancomycin," J. Biomed. Mater. Res. (1996) 33: 139-143; Otsuka et al., "A Novel Skeletal Drug Delivery System Using Self-Setting Calcium Phosphate Cement," J. Pharm. Sci. (November 1994) 83: 1569-1573; Otsuka et al., "A Novel Skeletal Drug Delivery System Using Self-Setting Calcium Phosphate Cement," J. Pharm. Sci. (May 1994) 83:611-615; Welch, "Antibiotics in Acrylic Bone Cement," J. Biomed Mater. Res. (1978) 12: 679-700; and Lautenschlager et al., "Mechanical Properties of Bone Cements Containing Large Doses of Antibiotic Powders," J. Biomed. Mater. Res. (November 1976) 10: 929-938.